The childhood hyperkinetic syndrome is a behavioral disorder affecting 4-10% of all school-age children. It consists of a number of cardinal features, including over activity, impulsivity, failure to habituate to novel environments, and other congitive learning problems. At present, the etiology of hyperkinesis in man is unknown. However, several animal models of hyperkinesis have been proposed, and the best among these models suggests that hyperkinesis is due to central dopamine denervation, resulting in denervation supersensitivity and an exaggerated or "paradoxical" response to amphetamine in hyperkinetics. Given that an important weight-loss confound can be eliminated in this model, it may prove useful to employ an animal model of hyperkinesis to determine the neuropharmacological mechanism responsible for hyperkinesis while suggesting treatments useful for the clinical management of hyperkinetic symptomatology. These treatment agents include amphetamine isomers, caffeine-amphetamine coadministration, and chronic lithium treatments. Converging support for the model may be provided by examining "reversible" models of hyperkinesis and the paradoxical response of amphetamine in post-synaptic dopamine receptor suspersensitivity states induced by caffeine and chronic neuroleptic treatments. Lastly, the effects of continued drug administration on residual learning deficits will be examined to suggest optimal treatment of previously overactive children.